Systems approach identifies HIPK2 as a critical regulator of kidney tubulointerstitial fibrosis

We used an integrated computational/experimental systems biology approach to identify upstream protein kinases that regulate gene expression changes in kidneys of HIV-1 transgenic mice (Tg26), which have significant tubulo-interstitial fibrosis (TIF) and glomerulosclerosis (GS). We identified the homeo-domain interacting protein kinase 2 (HIPK2) as a key regulator of TIF and GS. HIPK2 was upregulated in kidneys of Tg26 and patients with various kidney diseases. HIV infection increased the protein level of HIPK2 by promoting oxidative stress, which inhibited Siah1-mediated proteasomal degradation of HIPK2.

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Jin Y, Ratnam K, Chuang PY, Fan Y, Zhong Y, Dai Y, Mazloom AR, Chen EY, D'Agati V, Xiong H, Ross MJ, Chen N, Ma'ayan A, He JC